The proposed research deals with the metabolism, or biotransformation, of the characteristic chemical constituents of Cannabis sativa L. by selected microorganisms, comprising both fungi and bacteria. A number of microbes are being examined for their ability to effect hydroxylations and other metabolic transformation reactions on delta 9-tetrahydrocannabinol, delta 8-tetrahydrocannabinol, cannabidiol and cannabinol. Pure cannabinoids are incubated with growing vegetative cultures, resting cell suspensions or spores of microorganisms which are suspected of being able to form hydroxylated or other polar metabolites similar to those formed in mammalian systems. The microbial models of mammalian metabolism thus developed will be investigated as biological catalysts to be used in producing cannabinoid metabolites by fermentation. Results already obtained in this investigation indicate that such a fermentation synthesis could be scaled up to produce quantities sufficient to allow for pharmacological and toxicological testing. Particular emphasis will be placed on the mono- and dihydroxylated metabolites, carboxylic acids and hydroxy acids which are difficult to produce by conventional organic synthetic methods. Novel polar metabolites resulting from extensive modification of cannabinoids may provide clues to aspects of mammalian metabolism which are not yet understood. In addition, the biological oxidation reactions developed may be useful to other chemists who are engaged in the synthesis of novel physiologically active cannabinoids.